Role and mechanism of PVN-sympathetic-adipose circuit in depression and insulin resistance induced by chronic stress.

Chronic stress induces depression and insulin resistance, between which there is a bidirectional relationship. However, the mechanisms underlying this comorbidity remain unclear. White adipose tissue (WAT), innervated by sympathetic nerves, serves as a central node in the interorgan crosstalk through adipokines. Abnormal secretion of adipokines is involved in mood disorders and metabolic morbidities. We describe here a brain-sympathetic nerve-adipose circuit originating in the hypothalamic paraventricular nucleus (PVN) with a role in depression and insulin resistance induced by chronic stress. PVN neurons are labelled after inoculation of pseudorabies virus (PRV) into WAT and are activated under restraint stress. Chemogenetic manipulations suggest a role for the PVN in depression and insulin resistance. Chronic stress increases the sympathetic innervation of WAT and downregulates several antidepressant and insulin-sensitizing adipokines, including leptin, adiponectin, Angptl4 and Sfrp5. Chronic activation of the PVN has similar effects. ß-adrenergic receptors translate sympathetic tone into an adipose response, inducing downregulation of those adipokines and depressive-like behaviours and insulin resistance. We finally show that AP-1 has a role in the regulation of adipokine expression under chronic stress.

Chirality of exceptional points in bianisotropic metasurfaces.

In optical systems, one kind of exceptional point (EP) is associated with the maximally unidirectional reflection. Here, we theoretically show that the intrinsic chirality of this kind of EP is only determined by the sign of the scattering rate difference, and that these EPs could only be on or within a fundamental scattering bound in an asymmetric resonant system. As a proof of our theoretical deviation, a bianisotropic metasurface is designed to exhibit an extreme EP with a definite chirality on the fundamental scattering bound. In addition, another EP with the opposite chirality is also available within this scattering bound in the same metasurface without any additional symmetry operation. Numerical results are in good agreement with our theoretical predictions based on the coupled mode theory. We believe that our results not only provide physical insights to explore EPs in resonant systems, but also have implications in designing unidirectional absorbers and thermal emitters.

Kerr-nonlinearity induced bistable-like parity-time phase transition in coupled waveguides.

We analyze the parity-time (PT) symmetric phase in coupled two waveguides with a Kerr-type medium in between. Paying attention to the emitted field from a dipole source inside, we show that when the strength of the dipole increases, the optical Kerr effect can render a phase transition from the exact PT phase to the broken PT phase. Furthermore, a salient phenomenon of bistable-like PT phase is observed, in which the emitted field possesses a paradox between the two kinds of PT phases. We show that the physical mechanism of this bistable-like phenomenon is a globally inhomogeneous PT phase, in which different spatial regions of the whole structure can possess different PT phases (broken or exact). This study highlights the potential to manipulate the PT phase transition by using optical nonlinearity for many interesting applications.

Optical super-resonance in a customized P T-symmetric system of hybrid interaction.

We investigate the optical resonances in coupled meta-atoms with hybrid interaction pathways. One interaction pathway is the directly near-field coupling between the two meta-atoms. The other interaction pathway is via the continuum in a waveguide functioned as a common bus connecting them. We show that by properly introducing gain or loss into the meta-atoms, the hybrid optical system becomes parity-time (P T) symmetric, in which the effective coupling rate can be customized by manipulating the length of the waveguide. At the exact phase of the customized P T symmetry, the coupled meta-atoms support discrete super-resonant modes that can be observed from the transmission spectra as extremely sharp peaks. At an exception point where the eigenmodes coalesce, albeit the transmission curve is flat, a high-Q factor of the localized field in the meta-atoms can be obtained. Similarities of the super-resonance with the bound states in the continuum (BICs) are discussed. This investigation promotes our understanding about the ways in realizing high-Q optical resonance especially by manipulating the distributions of loss and gain via the concepts of P T and BICs. Many attractive applications are expected.

Hybrid parity-time modulation phase and geometric phase in metasurfaces.

We analyze the similarity between the geometric phase and the phase from parity-time symmetric modulation and argue that they can be integrated together in nanostructures. We provide a simple hybrid metasurface design to demonstrate the simultaneous utilization of these phases in manipulating the diffraction of optical field. Polarization-sensitivity of the hybrid phase is also discussed. This study provides a more advanced method of achieving polarization-dependent optical manipulation in artificial nanostructures.

Adiponectin modulates ventral tegmental area dopamine neuron activity and anxiety-related behavior through AdipoR1.

Adiponectin, a metabolic hormone secreted by adipocytes, can cross the blood-brain barrier to act on neurons in different brain regions, including those involved in stress-related disorders. Here we show that dopamine neurons in the ventral tegmental area (VTA) express adiponectin receptor 1 (AdipoR1). Intra-VTA infusion of adiponectin or the adiponectin mimetic AdipoRon in wild-type mice decreases basal dopamine neuron population activity and firing rate and reverses the restraint stress-induced increase in dopamine neuron activity and anxiety behavior. Adiponectin haploinsufficiency leads to increased dopamine neuron firing and anxiety behavior under basal conditions. Ablation of AdipoR1 specifically from dopamine neurons enhances neuronal and anxiogenic responses to restraint stress. The effects of intra-VTA infusion of adiponectin on neuronal activity and behavior were abolished in mice lacking AdipoR1 in dopamine neurons. These observations indicate that adiponectin can directly modulate VTA dopamine neuron activity and anxiety behavior, and that AdipoR1 is required for adiponectin-induced inhibition of dopamine neurons and anxiolytic effects. These results strengthen the idea of adiponectin as a key biological factor that links metabolic syndrome and emotional disorders.

Nonreciprocal parity-time phase in magnetized waveguides.

In a single magneto-optical (MO) waveguide, the dispersion of guided bulk wave is reciprocal in the Voigt configuration. Here we show that the parity-time (P T) phase in two coupled MO waveguides can be nonreciprocal if the waveguides are properly biased. The nonreciprocal P T phase is closely related to the asymmetric field profile induced by the MO effect that modifies the coupling strength between adjacent waveguides. We show that it is feasible to switch between broken and conserved P T phases by simply reversing the magnetic bias or the propagating direction of wave. Theoretical analysis and numerical calculation prove our theory. This investigation highlights a flexible method in manipulating the field dynamics of waveguide arrays by using the novel properties of P T phase especially the exceptional points.

Thioperamide attenuates neuroinflammation and cognitive impairments in Alzheimer's disease via inhibiting gliosis.

Alzheimer's disease (AD) is an age-related neurodegenerative disease, which characterized by deposition of amyloid-ß (Aß) plaques, neurofibrillary tangles, neuronal loss, and accompanied by neuroinflammation. Neuroinflammatory processes are well acknowledged to contribute to the progression of AD pathology. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. Recently, studies show that H3R are highly expressed not only in neurons but also in microglia and astrocytes. H3R antagonist has been reported to have anti-inflammatory efficacy. However, whether inhibition of H3R is responsible for the anti-neuroinflammation in glial cells and neuroprotection on APPswe, PSEN1dE9 (APP/PS1 Tg) mice remain unclear. In this study, we found that inhibition of H3R by thioperamide reduced the gliosis and induced a phenotypical switch from A1 to A2 in astrocytes, and ultimately attenuated neuroinflammation in APP/PS1 Tg mice. Additionally, thioperamide rescued the decrease of cyclic AMP response element-binding protein (CREB) phosphorylation and suppressed the phosphorylated P65 nuclear factor kappa B (p-P65 NF-κB) in APP/PS1 Tg mice. H89, an inhibitor of CREB signaling, abolished these effects of thioperamide to suppress gliosis and proinflammatory cytokine release. Lastly, thioperamide alleviated the deposition of amyloid-ß (Aß) and cognitive dysfunction in APP/PS1 mice, which were both reversed by administration of H89. Taken together, these results suggested the H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB-mediated gliosis and inflammation inhibiting, which contributed to Aß clearance. This study uncovered a novel mechanism involving inflammatory regulating behind the therapeutic effect of thioperamide in AD.

Role of Adiponectin-Notch pathway in cognitive dysfunction associated with depression and in the therapeutic effect of physical exercise.

A substantial percentage of late-life depression patients also have an cognitive impairment, which severely affects the life quality, while the co-occurring mechanisms are still unclear. Physical exercise can ameliorate both depressive behaviors and cognitive dysfunction, but the molecular mechanisms underlying its beneficial effects remain elusive. In this study, we uncover a novel adipose tissue to hippocampus crosstalk mediated by Adiponectin-Notch pathway, with an impact on hippocampal neurogenesis and cognitive function. Adiponectin, an adipocyte-derived hormone, could activate Notch signaling in the hippocampus through upregulating ADAM10 and Notch1, two key molecules in the Notch signaling. Chronic stress inhibits the Adiponectin-Notch pathway and induces impaired hippocampal neurogenesis and cognitive dysfunction, which can be rescued by AdipoRon and running. Inhibition Notch signaling by DAPT mimics the adverse effects of chronic stress on hippocampal neurogenesis and cognitive function. Adiponectin knockout mice display depressive-like behaviors, associated with inhibited Notch signaling, impaired hippocampal neurogenesis and cognitive dysfunction. Physical exercise could activate Adiponectin-Notch pathway, and improve hippocampal neurogenesis and cognitive function, while deleting adiponectin gene or inhibiting Notch signaling blocks its beneficial effects. Together, our data not only suggest that Adiponectin-Notch pathway is involved in the pathogenesis of cognitive dysfunction associated with depression, but also contributes to the therapeutic effect of physical exercise. This work helps to decipher the etiology of cognitive impairment associated with depression and hence will provide a potential innovative therapeutic target for these patients.

Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress.

Both genetic predisposition and life events, particularly life stress, are thought to increase the risk for depression. Reward sensitivity appears to be attenuated in major depressive disorder (MDD), suggesting deficits in reward processing in these patients. We identified the VTA-BLA-NAc circuit as being activated by sex reward, and the VTA neurons that respond to sex reward are mostly dopaminergic. Acute or chronic reactivation of this circuit ameliorates the reward insensitivity induced by chronic restraint stress. Our histological and electrophysiological results show that the VTA neuron subpopulation responding to restraint stress, predominantly GABAergic neurons, inhibits the responsiveness of VTA dopaminergic neurons to reward stimuli, which is probably the mechanism by which stress modulates the reward processing neural circuits and subsequently disrupts reward-related behaviours. Furthermore, we found that the VTA-BLA-NAc circuit is a positive feedback loop. Blocking the projections from the BLA to the NAc associated with sex reward increases the excitability of VTA GABAergic neurons and decreases the excitability of VTA dopaminergic neurons, while activating this pathway decreases the excitability of VTA GABAergic neurons and increases the excitability of VTA dopaminergic neurons, which may be the cellular mechanism by which the VTA-BLA-NAc circuit associated with sex reward ameliorates the attenuated reward sensitivity induced by chronic stress.

Joint influence of genetic origin and climate on the growth of Masson pine (Pinus massoniana Lamb.) in China.

Adaptive of trees and its correlation with the climatic are causing changes in tree species performance and distribution, which will change breeding programs and influence forest productivity. To further evaluate the joint influence of climatic factors and provenance on the ring width (RW) and ring density (RD) of Masson pine. We selected 18 provenances at Chun'an (CA) and Taizi Mountain (TZS) test site, which representing four different breeding regions, including the south, west, north and east-central regions. The results showed that the provenance effects were significantly for the RW and RD. The provenances from high temperature and low latitude regions had greater mean RW compared to species from local and cold sources. The geographical genetic variation in wood traits is generally weak. The correlation between RW of Masson pine and precipitation was stronger in the relatively arid TZS site compared with that in relatively wet CA site, as well as the effect of temperature and precipitation on RD was earlier than that in CA test site. The response relationship between establishing the width of tree rings and the environmental variables of provenance indicated that during the transition from the northern and western breeding regions to the eastern and southern breeding regions, the response of RW to climate factors changed from being temperature-based to being precipitation-based. In addition, the response of provenance to the climate of seed sources origin showed their own variation characteristics in each breeding area. Therefore, genetic improvement of big diameter wood and wood density can be gain through selection of provenance and analysis of adaptability.

Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin.

Sex differences in the incidence of depression and antidepressant treatment responses are well documented. Depression is twice as common in women as in men. Recent studies indicate that low levels of leptin, an adipocyte-derived hormone, are associated with increased symptoms of depression in women. Leptin has been shown to produce antidepressant-like effects in male rodents. In the present study, we examined sex differences and estrous cycle variations in antidepressant-like responses to leptin. Leptin administration significantly reduced immobility, a putative measure of behavioral despair, in the forced swim test in intact female mice in the proestrus phase but not in the diestrus phase of the estrous cycle. Moreover, leptin administration stimulated Akt phosphorylation in the hippocampus of female mice in proestrus but not in diestrus, in correlation with its differential behavioral effects in these two phases of the cycle. Leptin-induced behavioral responses and stimulation of hippocampal Akt phosphorylation in female mice were abolished by ovariectomy. By contrast, the antidepressant-like effect of leptin in male mice was not affected by gonadectomy (castration). Pretreatment with 17ß-estradiol restored sensitivity to the effects of leptin on behavior and hippocampal Akt phosphorylation in ovariectomized female mice. These results suggest leptin regulates depression-like behavior and hippocampal Akt signaling in a sex-specific and estrous cycle-dependent manner.